title: Cyclosporine versus everolimus: effects on the glomerulus.
abstract: Inhibitors of the mammalian target of rapamycin (mTOR) have been associated with proteinuria. We studied the development of proteinuria in renal transplant recipients (RTR) treated with the mTOR inhibitor everolimus in comparison with a calcineurin inhibitor. We related the presence of proteinuria to histopathological glomerular findings in two-yr protocol biopsies. In a single-center study, nested in a multicenter randomized controlled trial, we determined eGFR, proteinuria, and renal biopsy data (light- and electron microscopy) of RTR receiving prednisolone/everolimus (P/EVL) (n = 16) in comparison with patients treated with prednisolone/cyclosporine A (P/CsA) (n = 7). All patients had been on the above-described maintenance immunosuppression for 18 months. Renal function at two yr after transplantation did not differ between patients receiving P/EVL or P/CsA (eGFR 45.5 vs. 45.7 mL/min/1.73 m(2)). Proteinuria was slightly increased in P/EVL vs. P/CsA group (0.29 vs. 0.14 g/24 h, p = 0.06). There were no differences in light- or electron microscopic findings. We could not demonstrate increased podocyte effacement or changes in glomerular basement membrane (GBM) thickness in P/EVL-treated patients. In conclusion, long-term treatment with everolimus leaves the GBM and podocytes unaffected.
authors.affiliation: Renal Transplant Unit, Division of Internal Medicine, Department of Nephrology, Academic Medical Center, Amsterdam, the Netherlands. m.c.baas@amc.uva.nl
authors.forename: Marije C
authors.initials: MC
authors.lastname: Baas
authors.forename: Jesper
authors.initials: J
authors.lastname: Kers
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
authors.forename: Jaap J Homan
authors.initials: JJ
authors.lastname: van der Heide
authors.forename: Marius A
authors.initials: MA
authors.lastname: van den Bergh Weerman
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: ten Berge
authors.forename: Frederike J
authors.initials: FJ
authors.lastname: Bemelman
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use*; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery*; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000187:drug effects*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus
keywords: everolimus; glomerular basement membrane; mTOR inhibitor; podocytes; proteinuria